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Investigating the effects of chronic stress on hippocampal representations, synaptic connectivity and learning.

研究慢性压力对海马表征、突触连接和学习的影响。

基本信息

批准号：
324341049
负责人：
Dr. Alessio Attardo
金额：
--
依托单位：
Abteilung Zelluläre Neurowissenschaften
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/324341049?language=en
关键词：
Investigating effects chronic stress hippocampal

项目摘要

Stress is the most prominent environmental factor contributing to the pathophysiology of psychiatric diseases such as depression, schizophrenia, anxiety and post traumatic stress disorder. The detrimental effects of stress on cognition include dysregulation of learning and memory. Consistently with this, in humans and mice, stress alters the structure and physiology of the hippocampus, which is a brain region key for episodic memory. Although stress induces profound structural changes in the hippocampus, it still is unclear what are the effects of such changes on the ability of hippocampal neuronal networks to learn and recall information. This is mainly because, until now, it has been impossible to track neuronal activity in the same subjects over the typical durations of chronic stress and to investigate neuronal structure longitudinally in the hippocampus. To overcome these obstacles, I propose to use head mounted wide field optical imaging to track activity of thousands of CA1 hippocampal pyramidal neurons in freely behaving mice and to study spatial representations upon chronic stress. This will enable us to investigate stress-induced changes in spatial codes and impairment in learning and memory in the same animals longitudinally. Moreover, I plan to combine head mounted wide field with two-photon optical imaging to track cellular activity and synaptic connectivity in the same hippocampal CA1 pyramidal neurons over weeks. This will enable us for the first time to study the relationship between neuronal connectivity and activity under baseline and stressful conditions. By investigating how stress changes the way in which the hippocampus represents space this project will shed light on the fundamental mechanisms of learning and memory which will be important not only for basic but also for translational science.

压力是造成抑郁症、精神分裂症、焦虑症和创伤后应激障碍等精神疾病的病理生理的最突出的环境因素。压力对认知的有害影响包括学习和记忆的失调。与此相一致的是，在人类和小鼠中，压力改变了海马体的结构和生理学，海马体是情景记忆的关键大脑区域。虽然应激会引起海马结构的深刻变化，但目前还不清楚这些变化对海马神经元网络学习和回忆信息的能力有何影响。这主要是因为，到目前为止，还不可能在慢性应激的典型持续时间内跟踪同一受试者的神经元活动，并纵向研究海马体中的神经元结构。为了克服这些障碍，我建议使用头戴式宽场光学成像跟踪活动的数千个CA1海马锥体神经元在自由行为的小鼠和研究慢性应激的空间表示。这将使我们能够纵向研究相同动物中应激诱导的空间编码变化和学习记忆障碍。此外，我计划将联合收割机头戴式宽场与双光子光学成像相结合，以跟踪相同海马CA1锥体神经元中的细胞活动和突触连接数周。这将使我们第一次研究神经元连接和活动之间的关系，在基线和压力条件下。通过研究压力如何改变海马体代表空间的方式，该项目将揭示学习和记忆的基本机制，这不仅对基础科学而且对转化科学都很重要。